The influence of the SARS-CoV-2 lockdown on patients with inflammatory rheumatic diseases on their adherence to immunomodulatory medication: a cross sectional study over 3 months in Germany.

OBJECTIVES: To evaluate the influence of the SARS-CoV-2 pandemic on the adherence of patients with inflammatory rheumatic diseases (IRD) to their immunomodulatory medication during the three-month lockdown in Germany. METHODS: From 16th March until 15th June 2020, IRD patients from private practices and rheumatology departments were asked to answer a questionnaire addressing their behaviour with respect to their immunomodulating therapy. Eight private practices and nine rheumatology departments that included rheumatology primary care centres and university hospitals participated. A total of 4252 questionnaires were collected and evaluated. RESULTS: The majority of patients (54%) were diagnosed with RA, followed by psoriatic arthritis (14%), ankylosing spondylitis (10%), connective tissue diseases (12%) and vasculitides (6%). Most of the patients (84%) reported to continue their immunomodulatory therapy. Termination of therapy was reported by only 3% of the patients. The results were independent from the type of IRD, the respective immunomodulatory therapy and by whom the patients were treated (private practices vs rheumatology departments). Younger patients (<60 years) reported just as often as older patients to discontinue their therapy. CONCLUSION: The data show that most of the patients continued their therapy in spite of the pandemic. A significant change in behaviour with regard to their immunomodulatory therapy was not observed during the three months of observation. The results support the idea that the immediate release of recommendations of the German Society of Rheumatology were well received, supporting the well-established physician-patient relationship in times of a crisis.

[A cross sectional study on patients with inflammatory rheumatic diseases in terms of their compliance to their immunsuppressive medication during COVID-19 pandemic]. / Einstellung von Patienten mit entzündlich-rheumatischen Erkrankungen zur immunsuppressiven Therapie im Rahmen der COVID-19 Pandemie ­ eine Situationsanalyse.

The current COVID-19 pandemic inherits an unprecedented challenge for the treating rheumatologists. On the one hand, antirheumatic drugs can increase the risk of infection and potentially deteriorate the course of an infection. On the other hand, an active inflammatory rheumatic disease can also increase the risk for an infection. In the recommendations of the German Society for Rheumatology (www.dgrh.de), it is recommended that our patients continue the antirheumatic therapy to maintain remission or low state of activity despite the pandemic. In this study, patients with inflammatory rheumatic disease were asked in the first weeks of the pandemic on their opinion of their immunomodulating therapy. The result shows that over 90% of the patients followed the recommendation of the rheumatologist to continue the antirheumatic therapy, and only a small percentage of the patients terminated the therapy on their own. This result was independent of the individual anti-rheumatic therapy. Taken together, the results of this study illustrate not only the trustful patient-physician partnership in a threatening situation but also the high impact of state-of-the art recommendations by the respective scientific society.

Pathologic alterations of the heart and the kidney in patients with ankylosing spondylitis.

BACKGROUND: The occurrence of a variety of pathological lesions of the heart and kidneys have been described in patients with ankylosing spondylitis (AS). The frequency of these alterations and whether they are specific for AS has been discussed controversially. - METHODS: Outpatients with AS were studied to determine the frequency of cardiac and renal alterations and to assess the associated clinical and demographic factors. - RESULTS: A total of 77 patients with AS participated in the study (male 84.4%, mean age 48.3 +/- 1.5 years, mean duration of disease 15.4 +/- 1.2 years). Hypertension was present in 36.4% and diabetes mellitus in 13.0%. Impaired renal function (defined by a decrease in GFR) combined with markers of kidney damage suspective for chronic kidney disease were present in 3 patients (3.9%). Pathologic alterations of the heart were found in 25 patients (37.3%). Echocardiographic abnormalities were present in 20 patients (e.g. aortic and mitral insufficiency). Electrocardiographic abnormalities were present in 12 patients (e.g. atrioventricular, left and right branch block). Patients with cardiac abnormalities were older (54.2 +/- 2.9 vs. 44.9 +/- 1.7 years) and had a longer duration of disease (20.6 +/- 2.1 vs. 13.9 +/- 1.6 years) as compared to non-affected patients. - CONCLUSION: In our study, cardiac abnormalities were frequently seen in patients with AS, while renal disease was more rare and might be due to diseases not related to AS in most of patients. In contrast to cardiac involvement, it therefore appears questionable, that chronic kidney disease is part of the extraskeletal manifestations, or at least that AS has a high impact on renal integrity.

Opposite regulation of tissue factor expression by calcineurin in monocytes and endothelial cells.

Tissue factor (TF), the primary initiator of blood coagulation with structural homology to the cytokine receptor family, has been implicated in various vascular processes including metastasis, angiogenesis, and atherosclerosis. Within the vasculature, monocytes and endothelial cells (EC) can be activated to synthesize TF depending on the induction of NF-kappaB. Despite the undisputed value of cyclosporin A (CsA) as an immunosuppressant, problems have emerged due to induction of vascular changes by a poorly understood mechanism. We demonstrate that CsA has opposite effects on TF gene expression, inhibiting NF-kappaB-mediated TF gene transcription in monocytes but enhancing it in EC. To test whether CsA binding proteins (cyclophilins) can mediate these CsA effects we used a nonimmunosuppressant analog of CsA that binds to cyclophilins but does not inhibit the Ca2+/calmodulin-dependent phosphatase calcineurin (Cn). This drug lacked regulatory function for NF-kappaB and TF expression suggesting that Cn is responsible for the inverse gene regulation. The key function of Cn was supported by experiments demonstrating that other phosphatase inhibitors also either positively or negatively regulated NF-kappaB in monocytes and EC. Calcineurin was demonstrated to regulate NF-kappaB activation at the level of IkappaBalpha degradation, because agonist-induced phosphorylation and subsequent degradation of IkappaBalpha is prevented by Cn inhibitors in monocytes but enhanced in EC. These data identify Cn as an opposite regulator in generating transcriptionally active NF-kappaB, and they confirm the presumption that the ability of Cn to participate in NF-kappaB transactivation is not T cell specific.

Increased binding capacity of receptors for the epidermal growth factor in benign thyroid nodules and thyroid malignancies.

To determine the role of epidermal growth factor (EGF) receptors in thyroid tumorigenesis, EGF binding was compared in membranes from malignant and from benign thyroid tumors. Surgical specimens were obtained from 28 patients with thyroid carcinomas (3 papillary, 13 follicular, 6 undifferentiated, and 6 medullary carcinomas) and from 30 patients with benign thyroid tumors (15 scintigraphically functional and 15 nonfunctional nodules). In 30 cases normal tissue adjacent to the tumor was also obtained. EGF binding was seen to be increased not only in thyroid carcinomas but also in benign thyroid tumors, particularly in functional thyroid adenomas. The highest EGF binding was found in undifferentiated carcinomas. A direct comparison of the EGF binding characteristics in tumor and adjacent normal thyroid tissue revealed that the increased binding of EGF is due mainly to an increase in the number of binding sites rather than an alteration in receptor affinities. EGF binding capacities were 18.4 +/- 16.7 fmol/mg protein in thyroid carcinomas and 10.5 +/- 5.2 fmol/mg in the corresponding normal tissue (P < 0.05, Kd 0.84 +/- 0.26 nM, n = 11). In autonomously functioning thyroid adenomas binding capacities were 14.2 +/- 8.2 fmol/mg in the nodules and 8.9 +/- 4.8 fmol/mg in normal tissue (P < 0.01, Kd 0.73 +/- 0.62 nM, n = 15). In conclusion, EGF receptor levels are increased not only in malignant thyroid tumors but also in well-differentiated benign thyroid nodules.(ABSTRACT TRUNCATED AT 250 WORDS)